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TerminatedNCT01919346Updated Feb 27, 2018

Eculizumab for Prevention of Delayed Graft Function (DGF) in Kidney Transplantation

A Phase 2 interventional study of Eculizumab and Normal Saline in Delayed Graft Function, Kidney Transplantation and Complement Activity, sponsored by Heeger, Peter, M.D.. Terminated at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-02-27.

Sponsored by Heeger, Peter, M.D. · Phase 2, Interventional, and Prevention

Why this study was terminated
Based on results from Alexion PROTECT DGF study
Phase
Phase 2
Study type
Interventional
Enrollment
21
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to evaluate the efficacy of Eculizumab in the prevention of Delayed Graft Function following deceased donor kidney transplantation. Based on experimental data and supportive observations in humans associating complement gene upregulation with ischemic reperfusion (IR) injury, it is hypothesized that C5 cleavage is a key step in the pathogenesis of ischemic reperfusion injury following transplantation. It is further hypothesized that Eculizumab, a humanized monoclonal antibody that blocks C5 cleavage in humans will be an effective prophylactic agent to prevent IR injury in high risk recipients. This trial is a prospective, randomized study to test the efficacy of eculizumab vs. placebo given once at the time of transplantation and once again 24 hours later in preventing delayed graft function in first adult recipients of deceased donor kidneys.

02

Conditions studied

  • Delayed Graft Function
  • Kidney Transplantation
  • Complement Activity

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Keywords

  • Kidney Transplantation
  • Delayed Graft Function
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age 18 years or older
  • Weight > 40 kg
  • Male or Female
  • Recipient of first deceased donor kidney
  • Able to provide written informed consent
  • Transplant candidate as per site specific guidelines
  • Dialysis dependent renal failure (initiated more than 2 months prior to transplant)
  • Recipients of kidneys defined as:

    1. Extended Criteria Donor (ECD) kidney with brain death: Kidney donors 60 years of age or older; or donors aged 50-59 years and have two of the following features: Hypertension, terminal serum creatinine > 1.5 mg/dL, or death from cerebrovascular accident (CVA), OR
    2. Standard Criteria Donor (SCD) kidney with actual cold ischemia time (CIT) 18 - 40 hours

Exclusion criteria

Exclusion Criteria:

  • Patient is planned to receive a multi-organ transplant
  • Kidney from donor \< 6 years of age
  • Dual kidney transplant (from same donor, including en bloc)
  • Living donor kidney transplant
  • Recipients with donor-specific anti-HLA antibodies of more than 3,000 MFI
  • Participation in another investigational drug study
  • Recipient BMI > 40
  • ABO incompatible
  • DCD (donor with cardiac death) Donor
  • Women who are pregnant or breast-feeding
  • Women of child bearing potential who are unable or unwilling to use a medically acceptable form of contraception (defined as the use of oral, injected or implanted hormonal methods of contraception, intrauterine device (IUD)or intrauterine system (IUS), barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository)
  • Patients with HBsAg-positive status, HCV infection, or HIV infection
  • Patients with atypical hemolytic uremic syndrome (aHUS) or C3 glomerulonephritis (C3GN)
  • Active bacterial or other infection which is clinically significant in the opinion of the investigator
  • Patients with history of splenectomy
  • Patients with history of meningococcal disease
  • Patients allergic to or unable to tolerate Ciprofloxacin
  • Patients unable or unwilling to receive vaccination against meningitis prior to study drug administration
  • Patients with a known or suspected hereditary complement deficiency
  • Patients with a history of cancer (other than non melanoma skin cancers) within the last five years
  • Donors of more than 70 years of age
  • Subjects with a psychiatric or physical illness which in the opinion of the Investigator would interfere with their ability to participate in the study.
04

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Single group
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
21 participants (actual)

Study arms

  • Experimental
    Eculizumab

    Eculizumab 1200 mg (diluted in Sodium Chloride (NaCl) to 5mg/mL, volume = 240 mL) will be given intraoperatively at the time of transplantation prior to reperfusion of the renal allograft and again at 900 mg (diluted in NaCl to 5mg/mL, volume = 180 mL) 12-24 hours post-transplantation

    Drug: Eculizumab

  • Placebo comparator
    Normal Saline

    Administered at same volume and time as Experimental arm

    Drug: Normal Saline

Interventions

  • DrugEculizumab

    Also known as: Soliris

  • DrugNormal Saline
05

What researchers measure

Primary outcomes

  1. Hemodialysis

    The need of at least one dialysis treatment during the first 7 days after transplantation excluding: (i) requirement for a single dialysis session indicated for hyperkalemia (ii) hyperacute rejection, renal arterial and/or venous thrombosis, obstructive uropathy, recurrence of primary disease, and early thrombotic microangiopathy

    Time frame: 7 days post-transplantation

Secondary outcomes

  1. Estimated Glomerular Filtration Rate (GFR)

    Estimated GFR as determined from the 4-variable MDRD (Modified Diet in Renal Disease) equation on days 7, 30, 90 and 180 post-transplantation

    Time frame: 6 months post-transplantation

  2. Hemodialysis

    Number of dialysis sessions at 30 days and 8 weeks post-transplantation

    Time frame: 8 weeks post-transplantation

  3. Primary Non-function

    The incidence of primary non-function (PNF) defined as the need for dialysis-dependency for more than 8 weeks

    Time frame: 8 weeks post-transplantation

  4. Graft Rejection

    Incidence of graft rejection within 6 months

    Time frame: 6 months post-transplantation

  5. Patient Survival

    Patient survival at 12 months post-transplantation

    Time frame: 12 months post-transplantation

  6. Graft Survival

    Death censored graft survival at 12 months post-transplantation

    Time frame: 12 months post-transplantation

  7. Serum Creatinine

    Change from baseline in serum creatinine and serum creatinine concentration at 24, 48 and 72 hours post-transplantation

    Time frame: 3 days post-transplantation

  8. Urine Output

    Percentage of patients with total 24-hour urine output of more than 500 mL on post-transplantation days 2 and 3

    Time frame: 3 days post-transplantation

  9. Biomarkers

    Absolute levels of biomarkers associated with acute renal injury

    Time frame: 6 months post-transplantation

  10. Qualified Delayed Graft Function (qDGF)

    The incidence of qDGF defined as the requirement for dialysis for any reason in the first 7 days post-transplantation

    Time frame: 7 days post-transplantation

06

Study locations

5 sites
  • Yale - New Haven Hospital
    New Haven, Connecticut 06540, United States
  • Icahn School of Medicine at Mount Sinai
    New York, New York 10029, United States
  • Montefiore Medical Center
    New York, New York 10467, United States
  • University Hospitals Case Medical Center
    Cleveland, Ohio 44106, United States
  • Hospital of the University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
07

Registry details

Key details

Study ID
NCT01919346
Lead sponsor
Heeger, Peter, M.D.
Collaborators
Alexion Pharmaceuticals, Inc., Icahn School of Medicine at Mount Sinai
Responsible party
Sponsor
First posted
Aug 9, 2013
Start date
Aug 2013
Primary completion
Dec 2017
Completion
Dec 2017
Last update
Feb 27, 2018

Study contacts

Peter S Heeger, MD
principal investigator · Icahn School of Medicine at Mount Sinai

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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